Principles of General Physiology

The Normal Production of Heat.— A. V. and A. M. Hill (1913) find that, in adult or nearly full-grown rats, the fasting production is directly proportional to their weight. In the case of young animals, the proportion is more nearly to their surface, but is actually higher, compared with that of adults, than would be due to their relatively greater surface. This non-proportion of heat-production to body surface in rats shows that production is not regulated by actual loss alone, but that it is a consequence of necessary tissue activity. Miss A. M. Hill (1913) points out that if the heat production is determined by heat loss alone, the former should be proportional to the difference between the animal's temperature and the external temperature. If the difference is 22° (external temperature, 15°) the mean production was found to be 203 calories per gram per day. With a difference of 11° (external temperature 26°), instead of being half the previous one, the production was found to be 166 calories, or about four-fifths.

Macdonald (1913) finds in man at rest that the heat production is proportional to the surface, that is, to the two-thirds power of the weight. In work, the effect of weight decreases, or the heat production approaches more nearly to proportionality to weight, as would be expected, since the muscles make up so large a proportion of the weight. Effect of Food. — Fed animals show considerably more evolution of heat than fasting ones. The Regulation of Temperature. — In warm-blooded animals, where a delicate adjustment of rates of reactions to a particular temperature has been developed, it is clearly of great importance that means should be adopted to maintain this temperature at a constant level.

Let us see what means are available for the purpose. The production may be increased or decreased by muscular activity or rest ; but this, especially in high external temperatures, is somewhat limited in range, since a certain degree of muscular activity in respiration, heart beat and so on, must be continued. It is particularly effective in counteracting fall of external temperature. Next, we have very effective means of increasing loss of heat from the surface, including that of the mouth and respiratory passages. This may be done by dilatation of the blood vessels of the skin, mucous membrane, etc., but more effectively by evaporation of water, as pointed out on page 227 above. Hence we see the value of the sweat glands. Increased evaporation of water is also caused by increased rate of breathing, which has a direct cooling action on the mucous membrane of the respiratory passages. Conversely, loss of heat may be decreased by vascular constriction in the skin.'

It was pointed out by Fredericq (1882) that the cold to be struggled against comes from the outside and acts on sensory nerves in the skin ; whereas increased heat almost invariably arises in the organism itself and acts by raising the temperature of the blood, in that the centres of the sweat nerves and the vasodilator nerves are supposed to be excited by a rise of temperature. Naturally, the effect of external cold is also to cool, in a limited degree, the blood leaving the skin, but, since one of the means adopted to counteract cold is constriction of the blood vessels in the skin, thei'e must be comparatively little cooling of the blood. On the other hand, the external temperature very rarely rises above that of the warm-blooded animal, so that stimulation of cutaneous nerves will be secondary in this case, although not entirely excluded. Put in other words, the struggle against cold is preventive and obstructs loss of heat ; that against heat is rather curative and increases the loss of excess heat produced, rarely being able to diminish production to an effective extent. As regards this last point, it may be said to depend on the condition of the animal. If the surrounding temperature is /airly warm, the animal will be quiet and thus unable to diminish muscular contraction to a further extent when the temperature rises ; whereas, if the temperature is low, the animal is active and able to become quiet when the temperature rises.

Observations on the output of carbon dioxide form a very convenient means of estimating heat production and have been made much use of for this purpose. If we take an animal and measure its respiratory exchange when the temperature is at 15° in the room, the animal is active and we obtain a certain value; raise the surrounding temperature to about 30", the animal lies quiet and probably goes to sleep ; there is diminished production of heat shown by decrease of oxygen absorption and carbon dioxide output ; again, lower the surrounding temperature to about 0°, great muscular activity, with shivering, sets in and considerable increase of carbon dioxide output takes place.

These experiments can be done conveniently on a mouse with the apparatus described by Haldane (1892) and modified by Pembrey (1894) for use with small animals. Since the means adopted for regulation of temperature involve the bringing into play of so many and various kinds of efferent nerves, muscular, secretory, vasomotor, and so on, it is plain that a co-ordinating centre is a necessity. Experiments by Aronsohn and Sachs (1885) showed that puncture of the median side of the corpus striatum in the rabbit caused considerable rise in temperature. Further important experiments were made by Barbour (1912), who showed that application of heat or cold to the anterior end of the corpus striatum, in the region of the caudate nucleus, by means of a cylindrical metal tube through which water was circulated, caused definite changes in the body temperature. Any temperature below 33°, in the conditions of the experiments, acts as a cold stimulus and produces a rise in rectal temperature, together with shivering and vaso-constriction in the skin. Cold acts, then, as an exciting agent, like puncture, electrical stimulation, or the toxic substances of fever. Heat, on the other hand, that is, a stimulation temperature of 42°, in the conditions of the experiments, produces a fall in rectal temperature, muscular relaxation and dilatation of skin vessels (Fig. 140). It is to be presumed, also, that nerve impulses from the endings in the skin, sensitive to cold, are also in relation with the centre. No doubt, under normal conditions, the centre would be still more sensitive than in Barbour's experiments and would react to much smaller temperature changes in the blood. Barbour and Prince (1914) have shown that local heating of the centre causes diminution in the evolution of carbon dioxide, in the intake of oxygen and in the respiratory volume. Cooling the centre has opposite effects. The production

of heat is thus shown to be acted upon, as well as the loss of heat. Barbour and Wing (1913) have found that certain drugs known to produce fall or rise of body temperature, such as antipyrin, or /2-tetra-hydro-naphthylamine, respectively, act, when applied to the centre itself, in much smaller amount than when given intravenously. Antipyrin causes fall of temperature with increased respiration and, occasionally, vascular dilation in the ear of the rabbit ; quinine behaves similarly, with more marked vascular dilation. /3-tetra-hydronaphthylamine, on the other hand, causes rise of temperature, some shivering,

Fro. 140. CHANGES OF BODY TEMPERATURE PRODUCED BY WARMING AND COOLING THE H"EAT CENTRE IN THE REGION OF THE CORPUS STRIAT17M OF A. From one hour after insertion, at the arrow, of the tube apparatus for wanning and cooling the centre to five hours. Rise of temperature produced by the injury. During the period marked by the thin line above the curve — warm water passed through During the period marked by the thick line below curve — cold water causes rite of temperature. A second passage of warm water produces a, fall, During the night (dotted line) the fever due to the puncture of the centre returned, but was

B. The fever produced by the puncture gradually subsides and had disappeared next day. It was brought back by cooling the centre (thick line). An intermediate short period (thin line above) shows a rapid effect of wanning. great vascular constriction in the skin and restlessness, the effects on the heat centre being probably mixed with those on other centres. Evolution of Temperature Regulation. — According to the experiments of Vernon (1897), the carbon dioxide output of cold-blooded animals does not increase and decrease uniformly with increase and decrease of external temperature. There appears to be a region of temperature in which the output is nearly constant. Thus, on warming newts or earthworms from 10° to 22° '5, there is no increase in carbon dioxide output. This indicates some kind of control over heat production, probably in muscle, on the part of nerve centres more or less sensitive to change of temperature. A further stage of regulation is shown by the

Monotremes, as investigated by C. J. Martin (1901). Echidna is the lowest member of the scale of warm-blooded animals. If the external temperature changes from 5° to 35°, its temperature rises by 10°. In cold weather, it hibernates and its temperature is only half a degree above that of its surroundings. What regulation it possesses appears to be by change of production of heat. It possesses no sweat glands and exhibits no power of varying loss of heat by cutaneous vasomotor effects, nor does it increase its respiratory movements at high temperatures. The normal temperature of both Echidna and of Ornithorhynchus is 29° -8. In the latter, the temperature is maintained fairly constant, although low. It can modify both heat loss and heat production, but does not increase its respirations at high temperatures. Marsupials show a transition to higher mammals. Variation in production of heat is the ancestral method of adjustment ; by this means an animal combats fall of temperature. Later, a mechanism controlling loss of heat is developed, and thus rise of external temperature is compensated for, as well as the heat produced by the animal's own activity.

For further details, with regard to production and regulation of temperature, the article by Tigerstedt (1910) may be consulted. Many organs consisting of smooth muscle, and some with cross-striated muscle, such as the heart, exhibit, even when isolated from the influence of nerve centres, a continued series of periodic contractions and relaxations. From the facts detailed in the preceding pages, it is easy to see how a continuous stimulation might give rise to rhythmic contractions, owing to the refractory period.

Thus the ventricle of the frog's heart can be excited to rhythmic contraction by a constant current from a battery or by increase of intraventricular pressure. It may be supposed that the first application of the stimulus sets off a beat, but, for a time, the muscle is then inexcitable and, although the stimulus continues, it i8 ineffective. After the refractory period is past, the stimulus again becomes effective and excites a new beat and so on. It seems that the return of excitability has the same effect as a first closure of the current. Apparently, then, a constant stimulus is capable of accounting for rhythmic beats.

Another possibility to be taken into account is the using up of a store of excitable material, which has to be replaced and, when accumulated to a certain degree, discharges spontaneously. But certain objections may be made to this view. The manner in which rhythmical effects may arise by means of a nerve network may be read in the essay by von Uexkiill (1904). The production of rhythmic movements by discharges from the nervous system to skeletal muscles will be discussed in Chapter XVI.

We have seen already how changes of permeability give rise to rapid movements in plants by allowing escape of liquid from turgid cells. The majority of the usual movements of plants in response to light, gravity, etc., although initiated by changes of permeability, are fixed in their results by different rates of growth on the opposite sides of the moving parts. It is stated that movements due to growth, such as those of tendrils, are considerably more rapid than might be supposed, being detectable in a minute or two. The first stage of many movements is an osmotic one, as remarked, due to changes of permeability and, hence, of turgor. In such a stage, if placed in strong saline solutions, which abolish the turgor on both sides, the curvature is done away with. At a later stage, the curvature is permanent and due to growth.

There is a point of resemblance between the mechanism of plant and animal movements, otherwise apparently so different, to which attention may be called. The immediate source of the energy of the movement is, in both cases, surface and osmotic energy, although, of course, the ultimate one in the green plant is the sun's radiation and, in the animal, oxidation of material derived from plant life. In the last resort, the animal's energy is also derived from the sun.

Details of the movements of plants and the interesting facts in connection therewith will be found in Pringsheim's book (1912). In the methods of analysing the forms of muscular contraction, we have, for the first time in the present book, come across a systematic use of the graphic method, so that a few words on the subject may not be out of place here. Any representation of the relation of two phenomena to one another by drawing a curve on squared paper is, of course, a "graph." But the name "graphic method" in physiology is especially used to refer to cases where the curve is drawn by the apparatus used to observe the phenomenon. The abscissa; are nearly always time, the curve being made on a moving surface.

This surface may be of glazed paper or of glass, in either case smoked by a flat flame, supplied with gas which has passed over cotton wool wet with benzene. In this way, sufficient smoke can be deposited without burning the paper, if this is moved rapidly through the flame by rotating the drum or other surface on which the paper is fixed. Although the present book is not primarily intended as a laboratory guide, it may be useful to mention that, when the force moving the point which scratches away the smoke is very small, such as that of the frog's auricle, it will be found very important to have as little friction as possible between the paper and the point. In such cases, the form of tracing point devised by mj'self (1912, 1) will be found useful. Bose (1913) has worked out a delicate method for tracing the movements of such structures as those of the leaves of sensitive plants, which have very little force. The friction of the tracing point on the recording surface is practically abolished, by causing it to vibrate rapidly in a plane perpendicular to the surface, so that contact takes place only momentarily. This vibration is effected by an electromagnetic arrangement.

The nature of the varnish used for fixing the curves is not a matter of indifference. Ten per cent, shellac in 90 per cent, alcohol, or ordinary white hard varnish, diluted with an equal volume of alcohol, serves well, but, in either case, it is better to add a few cubic centimetres of castor oil to the litre to prevent brittleness when dry. The tracing should be quite dry when the varnish is applied, by drawing the paper through it, and it should be allowed to harden in a dry atmosphere. Further information is to be found in the article by Frank (1911).

Photographic methods have many advantages. A beam of bright light is reflected from a mirror attached to the moving part of the apparatus ; any inertia can thus be avoided. The beam is passed through a slit and forms a point of light on a moving sensitive surface, paper or plate, behind the slit. Sometimes the shadow of a small moving part is projected on to the slit by means of a microscope, as in the " string " galvanometer. Details of the various methods will be found in the article by Garten (1911).

An excellent form of photographic registration apparatus for paper or plates is that made by the Cambridge Scientific Instrument Company for use with the "string" galvanometer, but is available for any form of photographic method. In the animal, there are certain tissues, known as muscular, which have the function of causing movement of parts relative to one another or, if the ends are so fixed that no change of place can occur, a state of tension is developed.

There are two chief classes of contractile tissue — the cross-striated, skeletal, which is dependent on impulses from the central nervous system to set it into activity, and the smooth, or involuntary, muscle also under the control of the central nervous system, but capable of exerting an automatic, tonic contraction or a rhythmic series of contractions. The latter class of muscular tissues, although subject to reflexes, are not under voluntary control. The muscular coat of the arterioles and the heart are examples of this class.

The rate of contraction of smooth muscle is slower than that of skeletal muscle ; but numerous varieties occur in both, so that the extreme cases do not greatly differ. The intimate structure of muscle fibre is very difficult to investigate. The dark bands seen in cross-striated muscle are doubly refracting. In the state of contraction, the dark and light bands appear to change places ; but the position of the doubly refracting part does not change, so that it is the light band which is doubly refracting in this state. According to Engelmann, in contraction the doubly refracting part increases in volume at the expense of fluid derived from the singly refracting part. The property of double refraction is, according to Engelmann, associated with the power of contractility as a general rule in the animal kingdom.

The production of tension is the essential point in the mechanics of muscular contraction. The muscle changes its properties from those of an unstretched steel spring to those of a stretched one, without necessarily changing its length. Various modes of contraction may be obtained from muscle, according to whether it is allowed to shorten or not, or the phase of the contraction at which the muscle is allowed to shorten, or at which the load is applied or removed.

An isolated muscle can be made to do external work by raising a weight, which is prevented from falling again. This is done by a mechanism known as the "work collector." The work done by an animal is measured by some form of " ergometer." A stimulus applied before the effect of a previous one has disappeared produces a contraction which is itself less than the previous one, but takes its origin from a shorter state of the muscle. Since the effect of each is less than that of its predecessor, a stage is reached beyond which no further shortening takes place. If the stimuli succeed one another at a rate such that the muscle has not commenced to relax before the next stimulus arrives, we have a smooth continuous curve. The phenomenon described is known as the " summation of contractions," producing "tetanus."

This tetanus is also the condition of skeletal muscle when excited by impulses from the cells in the nerve centres. The rate at which these impulses are sent out is, in man, from forty-seven to fiftyeight per second. In the tortoise, the rate is a linear function of temperature between 4° and 40°, like that of t"he mammalian heart between 27° and 40°. A resting excitable muscle is a physico-chemical system possessing potential energy. When stimulated, this potential energy is converted into energy of tension, which can then be used for the performance of work, or allowed to become degraded into heat.

This contractile process itself is associated with the splitting off of lactic acid, but there is neither consumption of oxygen nor evolution of carbon dioxide. It is not an oxidation process. To restore the potential energy which the system has lost in contracting,* energy is supplied by another reaction of a chemical nature, which succeeds the contractile stage. The lactic acid is put back into its original place in the course of this second process.

The energy required for the second process is afforded by a reaction in which some substance, carbohydrate or fat, is oxidised. Much oxygen is used, and carbon dioxide given off. The energy developed in contraction, as measured by the heat into which it is converted, is directly proportional to the tension produced. It is proportional to the length of the fibres at the time the contractile process takes place and not to their volume. It is, therefore, a surface phenomenon. Osmotic energy may, nevertheless, intervene as a further step, being controlled by the products of the change in surface energy.

The fact that the reaction by which the energy of the contractile system is restored is one having, apparently, no chemical component in common with the contractile system itself, indicates that this latter is not a chemical system, but one of a more physical nature. The nature of its energy as that of surfaces is also confirmed by the fact that it has a negative temperature coefficient, while all other possible forms of energy involved in muscular contraction have a positive one.

The muscular system is analogous to that of a gas engine used to compress air into a reservoir, from which it is taken to drive, by its pressure, various machines and tools. The energy of the oxidation of the fuel is not used from the engine directly. There is reason to believe that it is the lactic acid or its hydrogen ions that is responsible for the changes in surface energy. The question of the origin of the lactic acid required to replace that lost to the blood in vigorous muscular exercise, owing to deficient oxygen supply, is not yet decided.

The "efficiency" of the first, contractile, phase is practically 100 per cent., that is, the whole of the tension developed can be used for work. That of the whole process only amounts to about 50 per cent., since part of the chemical energy of the oxidation process of the restoration period is lost as heat. The efficiency of the act of maintaining tension, as by holding up a weight, is much less. This fact renders the calculation of the efficiency of the whole animal or of an isolated organ, such as the heart, a matter of difficulty.